Effects of Hypobaric Conditions on Apoptosis Signalling Pathways in HeLa Cells

Arican, Gul Ozcan,Khalilia, Walid,Serbes, Ugur,Akman, Gizem,Cetin, Idil,Arican, Ercan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Nowadays increasing effectiveness in cancer therapy and investigation of formation of new strategies that enhance antiproliferative activity against target organs has become a subject of interest. Although the molecular mechanisms of apoptosis can not be fully explained, it is known that cell suicide program existing in their memory genetically is activated by pathophysiological conditions and events such as oxidative stress. Low pressure (hypobaric) conditions that create hypoxia promote apoptosis by inhibiting cell cycling. In this study, determination of the effects of fractional hypobaric applications at different times on HeLa cells at cellular and molecular levels were targeted. Experiments were carried out under hypobaric conditions (35.2 kPa) in a specially designed hypobaric cabin including 2% $O_2$ and 98% N. Application of fractional hypobaric conditions was repeated two times for 3 hours with an interval of 24 hours. At the end of the implementation period cells were allowed to incubate for 24 hours for activation of repair mechanisms. Cell kinetic parameters such as growth rate (MTT) and apoptotic index were used in determination of the effect of hypobaric conditions on HeLa cells. Also in our study expression levels of the Bcl-2 gene family that have regulatory roles in apoptosis were determined by the RT-PCR technique to evaluate molecular mechanisms. The results showed that antiproliferative effect of hypobaric conditions on HeLa cells started three hours from the time of application and increased depending on the period of exposure. While there was a significant decrease in growth rate values, there was a significant increase in apoptotic index values (p<0.01). Also molecular studies showed that hypobaric conditions caused a significant increase in expression level of proapoptotic gene Bax and significant decrease in antiapoptotic Bfl-1. Consequently fractional application of hypobaric conditions on HeLa cell cultures increased both antiproliferative and apoptotic effects and these effects were triggered by the Bax gene.

Do Statins Counteract the Effect of Antidiabetic Drugs? Results of the SCEAD Study

Bahar Arican Tarim,Francesco Fici,Istemihan Tengiz,Saadet Avunduk,Yurdaer Ozcan,Gokhan Faikoglu,Elif Ari,Nicolás Roberto Robles,Guido Grassi 연세대학교의과대학 2023 Yonsei medical journal Vol.64 No.3

Purpose: Diabetes and dyslipidemia are leading causes of mortality and morbidity. According to international guidelines, statins are the cornerstone of treatment in patients with diabetes and/or dyslipidemia. However, statins and antidiabetic agents have op posite pharmacological effects, because statins, particularly atorvastatin and rosuvastatin, impair glucose homeostasis, increas ing the risk of new-onset diabetes, whereas antidiabetic drugs improve glycemic homeostasis. The aim of this study was to inves tigate the effect of atorvastatin, rosuvastatin, and pitavastatin on glucose homeostasis in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia during stable treatment with hypoglycemic drugs. Materials and Methods: The study was conducted as a pilot, prospective, randomized, open label, parallel group with blinded endpoints (PROBE) study. Of 180 recruited patients with T2DM and dyslipidemia, 131 were randomized to atorvastatin (n=44), rosuvastatin (n=45), and pitavastatin (n=42) and treated for 6 months. Results: Fasting plasma glucose (FPG) marginally decreased in patients assigned to atorvastatin (-3.5 mg/dL, p=0.42) and rosuvas tatin (-6.5 mg/dL, p=0.17), while it decreased much more in patients treated with pitavastatin (-19.0 mg /dL, p<0.001). Mean gly cated hemoglobin A1c (HbA1c ) values remained unchanged during treatment with atorvastatin (-0.10%, p=0.53) and rosuvastatin (0.20%, p=0.40), but were significantly reduced with pitavastatin (-0.75%, p=0.01). Atorvastatin, rosuvastatin, and pitavastatin sig nificantly lowered (p<0.001) plasma levels of total cholesterol, low-density lipoprotein-cholesterol, and triglycerides, while high density lipoprotein-cholesterol (HDL-C) levels increased significantly (p=0.04) only in the pitavastatin group. Conclusion: The results of the present study suggest that pitavastatin affects FPG and HbA1c less than atorvastatin and rosuvas tatin in patients with T2DM and concomitant dyslipidemia. Lipid-lowering efficacies were not significantly different among the three statins, with the exception of HDL-C, which increased significantly with pitavastatin. Although the pharmacological mecha nism of pitavastatin on glucose homeostasis in patients with T2DM during stable antidiabetic therapy is not known, it can be as sumed that pitavastatin has less drug interaction with hypoglycemic agents or that it increases plasma levels of adiponectin.

Effect of the Pruritus on the Quality of Life: A Preliminary Study

( Irem Eren Erturk ),( Ozer Arican ),( Imran Kurt Omurlu ),( Necdet Sut ) 대한피부과학회 2012 Annals of Dermatology Vol.24 No.4

Background: Pruritus affects the quality of life (QoL) in the patients. However, little is known of the impacts of itching on the QoL in the literature. Objective: In this study, a questionnaire eliciting specific responses about pruritus was used to determine the effect of itching and its severity on QoL in chronic pruritic patients. Methods: One hundred ten adult patients with chronic pruritus were surveyed. Once itch severity had been self-reported by patients, together with Skindex-29, they have been given the 18-item Pruritus- related Life Quality Index (PLQI) questionnaire, which was used to generated the new index. Results: Significant correlations have been found between the pruritus severity score of participants and their total Skindex-29 (p<0.001) with its function, emotion and symptom subscale scores (p <0.001 for each). Also, significant correlations were evident between total PLQI (p<0.001) and its psychosocial negativities, difficulties in everyday activities and social live subscale scores (p<0.001 for each). In particular, the emotion subscale of Skindex-29 (p=0.02) and psychosocial negativity subscale of PLQI (p=0.02) were significantly high in psychopathologic patients. A highly positive statistical correlation between Skindex-29 and PLQI scales was evident (r=0.845, p<0.001). For reliability, Cronbach`s coefficient a coefficients were 0.931 for the Skindex-29 scale and 0.918 for the PLQI scale. Conclusion: The results demonstrate that chronic pruritus appreciably reduces the QoL. PLQI could be used in the development of new questionnaires for determining the QoL of patients with chronic itch. (Ann Dermatol 24(4) 406∼412, 2012)

Carcinosarcoma of the Renal Pelvis and Urinary Bladder : A Case Report

Yilmaz, Erkan,Birlik, Bilge,Arican, Zumre,Guney, Soner Korean Radiological Society 2003 Korean Journal of Radiology Vol.4 No.4

Lack of Prognostic Significance of C-erbB-2 Expression in Low- and High- grade Astrocytomas

Muallaoglu, Sadik,Besen, Ali Ayberk,Ata, Alper,Mertsoylu, Huseyin,Arican, Ali,Kayaselcuk, Fazilet,Ozyilkan, Ozgur Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Background: Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Materials and Methods: Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Results: Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Conclusions: Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

Primary Extranodal Non-Hodgkin's Lymphoma: Clinicopathological Features, Survival and Treatment Outcome in Two Cancer Centers of Southern Turkey

Mertsoylu, Huseyin,Muallaoglu, Sadik,Besen, Ayberk Ali,Erdogdu, Suleyman,Sezer, Ahmet,Sedef, Ali Murat,Kose, Fatih,Arican, Ali,Ozyilkan, Ozgur Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkin's lymphoma (pENL) patients, focusing on treatment and survival outcome. Materials and Methods: Between October 2003 and March 2012, 802 patients with non-Hodgkin's lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. Results: pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5-1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. Conclusions: Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis.